Hyperpolarized ⁸⁹Y-EDTMP complex as a chemical shift-based NMR sensor for pH at the physiological range.

Area of Science:

• Nuclear Magnetic Resonance (NMR) Spectroscopy
• Medical Imaging (MRI)
• Inorganic Chemistry

Background:

• Yttrium (III) complexes share similarities with Gadolinium (Gd3+) complexes used in MRI contrast agents.
• While Gd3+ agents use T1/T2 relaxation, Yttrium (Y3+) complexes can utilize chemical shift changes for quantitative MRI.
• Conventional 89Y NMR/MRI faces challenges due to low sensitivity and long T1 relaxation times.

Purpose of the Study:

• To investigate the feasibility of using hyperpolarized 89Y-complexes as chemical shift-based pH NMR sensors.
• To evaluate 89Y-EDTMP and 89Y-DTPMP as potential pH sensors in biological conditions.
• To compare the pH sensing capabilities of novel 89Y-complexes with existing sensors like 89Y-DOTP.

Main Methods:

• Dissolution dynamic nuclear polarization (DNP) to enhance 89Y NMR/MRI signal sensitivity.
• Synthesis and characterization of 89Y-EDTMP and 89Y-DTPMP complexes.
• DNP-NMR experiments and pH titration studies to determine pKa and chemical shift dispersion.

Main Results:

• Hyperpolarized 89Y-DTPMP exhibited an apparent pKa of ~7.01 with a 4 ppm chemical shift dispersion.
• Hyperpolarized 89Y-EDTMP showed an apparent pKa of 6.7 with a 16 ppm chemical shift dispersion across pH 5-9.
• Compared to 89Y-DOTP (pKa 7.64, ~10 ppm dispersion), 89Y-EDTMP demonstrated a wider chemical shift range at physiological pH.

Conclusions:

• Hyperpolarized 89Y-EDTMP shows enhanced pH sensing capabilities within the physiological pH range.
• These findings suggest potential for 89Y-EDTMP as a quantitative MRI-based pH sensor.
• The use of DNP significantly overcomes the inherent low sensitivity of the 89Y nucleus for NMR/MRI applications.